HAART has altered the face of neurologic disease in people living with HIV-1, slowing its onset, and even in some cases reversing symptoms. Unfortunately, HAART has not altered the prevalence of neurologic disease, thus we hypothesize there is a reversible metabolic component of HIV-1 associated neurologic disease with molecular targets that we can define in laboratory models, design rational adjunctive neuroprotective drugs for, either singly or in combination, then test in in vitro and in vivo models of neuroAIDS, and ultimately bring the most successful of these strategies to Phase 1 trials within the award period of this grant.